The dermis is one of the three constituent layers of the skin contained between the epidermis and hypodermis. The dermis is conjunctive tissue underpinning the skin and is chiefly composed of an extracellular matrix (ECM) produced by fibroblasts which are the main cell population of the dermis.
The extracellular matrix is composed of protein fibres (collagen and elastin) and of an extrafibrillar matrix also known as the fundamental substance comprising inter alia structural glycoproteins (fibronectin) and proteoglycans/glycosaminoglycans. Collagens represent about 70% of ECM components with type-I collagen in majority (85 to 90% of dermal collagen) and type-III collagen (10-15% of dermal collagen). Collagens impart firmness to the dermis with resistance to pressure (mechanical strength of the skin). Elastin fibres impart elastic properties thereto.
While collagens are essential for maintaining skin firmness, the role of the epidermal-dermal junction (EDJ) is not to be neglected. The EDJ is a complex structure separating the dermis from the epidermis. Its chief functions are those of providing mechanical support for adhesion of the epidermis to the dermis, and acting as diffusion barrier and exchange region between the two compartments. Adhesion of the epidermis to the dermis is ensured inter alia by anchoring proteins such as type-IV collagens or laminin 5. When the dermis adheres less to the epidermis, the skin loses firmness and the epidermis slackens and creases.
Glycation is a well-known phenomenon at skin level, in particular at the dermis. It is a spontaneous, non-enzymatic reaction between an amine group, in particular an amine group of an amino acid forming the proteins e.g. lysine, and a reducing sugar such as glucose or ribose.
At the dermis, glucose particularly reacts with collagen and/or elastin to yield compounds causing so-called “advanced glycation end products”, well-known under the abbreviation “AGEs”. These chemical modifications are not without consequences on the properties of collagen and/or elastin. For example, AGEs induce the formation of molecular bridging between the collagen fibres. These bridges deteriorate the mechanical properties of the collagen fibres by making them more rigid.
The glycation phenomenon may therefore affect the proteins of the dermal extracellular matrix such as collagen and thereby deteriorate the metabolic and mechanical properties thereof.
At skin level, since glycation deteriorates the organisation of collagen fibres and the functionalities of the dermal fibroblasts (such as the ability to contract within collagen lattices), loss of tissue firmness and elasticity is observed. The skin loses it firmness and becomes slackened. Glycation of proteins, and of collagen in particular, therefore leads to harmful consequences for the skin. These consequences can be visibly seen and may be more or less unsightly. In particular, being less structured, less firm the dermal tissue has lesser resistance against the growth of adipocytes located in the hypodermis, creating a dimpled appearance known as “orange peel”.
There is therefore a need to find agents allowing the prevention of loss of skin firmness or an increase in skin firmness. Advantageously, said agent would allow the prevented onset of skin dimpling or a reduction in the orange peel appearance of the skin, in particular in persons with cellulite.